Presbyopia, occurring after middle age, is the inability of an eye to focus correctly. This age-related ocular pathology manifests itself in a loss of accommodative ability. Accommodative ability is the capacity of the eye, through the lens, to focus on near or far objects by changing the shape of the lens to become more spherical, or convex. A person may be a myopic presbyope or a hyperopic presbyope.
The ciliary muscle controls the shape of the lens through suspended suspensory ligaments called zonules. Like most smooth muscles, the ciliary muscle has a dual innervation, receiving both sympathetic and parasympathetic fibers.
In the ciliary muscle, the contraction necessary for accommodation is under parasympathetic or cholinergic control. While this parasympathetic control is predominant, sympathetic, or adrenergic, innervation opposes the cholinergic control and plays a lesser role in enabling relaxation of the ciliary muscle.
Most current theories of accommodation assume that the condition of physiological rest of accommodation occurs when the emmetropic eye focuses on a distant target, demanding good resolution. The fact that the optical value for the location of this distant target can be stated as zero diopters from the eye has tended to perpetuate the concept that active accommodation is unidirectional toward a near object.
However, if one considers that if the normal stimulus to accommodation is visual in nature, then the resting state of the eye must be determined by removing all visual stimuli, as for example, in complete darkness or in a luminous but completely empty visual field. This state of rest of the eye has been called xe2x80x9ctonic accommodationxe2x80x9d, xe2x80x9cspace myopiaxe2x80x9d and xe2x80x9csky myopiaxe2x80x9d, and averages about 1 D in extremely low illumination or total darkness but may be as high as 2 D myopia.
This implies that the resting state of accommodation is present when the eye is focused for objects about one meter away. Accordingly, distant objects would be focused on the retina by an active negative accommodation and near objects would be focused by an active positive accommodation.
Accordingly, in the natural resting state of the eye, the parasympathetic/cholinergic system maintains ciliary muscle tone, i.e., the ciliary muscle is contracted and zonular tension is relaxed such that the lens is more spherical and in a forward position increasing the refractive power of the eye. Thus, the eye is naturally in a xe2x80x9ctonic accommodativexe2x80x9d state and with appropriate stimulus is capable of further active positive accommodation as well as active negative accommodation.
A method in accordance with the present invention provides for increasing or decreasing parasympathetic/cholinergic/ciliary tonic contraction in order to restore the resting position of the eye and allow normal positive and negative accommodation for both myopic and hyperopic presbyopes. This action of the ciliary muscle under parasympathetic innervation provides for zonules relaxation which allows the lens to assume a more spherical shape.
A specific method in accordance with the present invention comprises administering to a presbyopic subject an effective amount of a muscarinic agonist or antagonist.
The agonist/antagonist is administered in a pharmaceutically acceptable ophthalmic formulation, preferably the agonist is administered topically by application of the formulation to the eye in a non-irritating sterile solution or suspension. In that regard, the formulation is preferably at a pH compatible with the eye. More particularly, in accordance with the present invention, a muscarinic agent may be selected to act on various M receptors of the ciliary muscle.